Year: 2010
Type: article
Abstract: Despite the progress of the past two decades, the cause of Alzheimer's disease (AD) and effective treatments against it remain elusive. The hypothesis that amyloid-β (Aβ) peptides are the primary causative agents of AD retains significant support among researchers. Nonetheless, a growing body of evidence shows that Aβ peptides are unlikely to be the sole factor in AD etiology. Evidence that Aβ/amyloid-independent factors, including the actions of AD-related genes, also contribute significantly to AD pathogenesis was presented in a symposium at the 2010 Annual Meeting of the Society for Neuroscience. Here we summarize the studies showing how amyloid-independent mechanisms cause defective endo-lysosomal trafficking, altered intracellular signaling cascades, or impaired neurotransmitter release and contribute to synaptic dysfunction and/or neurodegeneration, leading to dementia in AD. A view of AD pathogenesis that encompasses both the amyloid-dependent and -independent mechanisms will help fill the gaps in our knowledge and reconcile the findings that cannot be explained solely by the amyloid hypothesis.
Source: Journal of Neuroscience
Institutions: Cleveland Clinic, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Nathan Kline Institute for Psychiatric Research, New York University, NYU Langone Health, Icahn School of Medicine at Mount Sinai, Howard Hughes Medical Institute, Harvard University, Massachusetts Institute of Technology, Brigham and Women's Hospital
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Awards: G1029799266, G1368710259, G1583914015, G433378027, G4413538008, G4961683883, G521617777, G646632903, APP/APLP1/APLP2 in the brain, G656934695, The In Vivo Role of AICD in Neuronal Dysfunction, Cell and Molecular Pathobiology of Alzheimer's Disease, G8544580608, G9000009683, G9000023224, G9000053895, G9000313348, G9000317024, G9000345308, G92896382, G998370925
OpenAlex ID: W2018494194